Hepatic cholesterogenesis in Chileans with cholesterol gallstone disease. Evidence for sex differences in the regulation of hepatic cholesterol metabolism.

To test the hypothesis that hepatic cholesterol synthesis and concentration are specifically increased in women and men with cholesterol gallstone disease, we studied in a series of 24 surgical liver biopsy specimens, the rate of acetate incorporation into cholesterol and CO2, and the concentration of free and esterified cholesterol. There were 6 women in each group of 12 control and 12 gallstone patients. Therefore, hypersecretion of biliary cholesterol, a common finding in Chileans with gallstones, is not pathologically linked to a basic biochemical abnormality in the hepatic cholesterogenic pathway. The concentrations of hepatic cholesterol were similar in patients with and without gallstones. However, there were significant increments of 37% in the free fraction and 78% in the esterified fraction of hepatic cholesterol in female subjects, irrespectively of the presence of cholelithiasis. These results suggest that the flux of lipoprotein cholesterol to the liver is increased in women. The regulatory mechanism of hepatic cholesterogenesis is less sensitive to cellular cholesterol in women than in men, as the fluxes of acetate into cholesterol are similar to both sexes, in spite of the significant increase of hepatic cholesterol in females. These findings demonstrate that sex factors play a fundamental role in the regulation of cholesterol metabolism in the human liver.